Interestingly, it was reported that S100A4 could enhance STAT3 phosphorylation,18,19 and STAT3 phosphorylation (p-stat3) was correlated with OPN expression.20 In addition, STAT3 was predicted to be a potential transcription factor of OPN.21 Therefore, we further evaluated OPN, STAT3, and STAT3 phosphorylation levels in S100A4 knockdown HCC-LM3 and MHCC97-H cells and in S100A4 overexpressed Huh7 and PLC cells, and found that OPN and STAT3 phosphorylation levels significantly changed in accordance with S100A4 levels (Fig. 5a). Here, SPP1 is linked to hepatocellular carcinoma.